Results of FRESCO trial of fruquintinib, a proposed treatment for colorectal cancer, presented by Chi Med at ASCO.

Hutchison China MediTech Limited (“Chi-Med”) announced at ASCO that results from its pivotal Phase III trial with fruquintinib, its novel vascular endothelial growth factor receptor (“VEGFR”) kinase inhibitor, were highlighted in an oral presentation during the American Society of Clinical Oncology Annual Meeting (“ASCO”), held in Chicago.

Results showed that FRESCO, a randomized, double-blind, placebo-controlled, multi-centered Phase III trial assessing fruquintinib in patients with locally advanced or metastatic colorectal cancer (“CRC”) in China, met all primary and secondary endpoints including significant improvements in overall and progression-free survival with a manageable safety profile and lower off-target toxicities compared to other targeted therapies.

Efficacy Results- The FRESCO trial is a randomized, double-blind, placebo-controlled, multicenter, Phase III pivotal trial in patients with locally advanced or metastatic CRC who have failed at least two prior systemic antineoplastic therapies, including fluoropyrimidine, oxaliplatin and irinotecan. No drugs have been approved in third-line CRC in China, with best supportive care (“BSC”) being the general standard of care. Enrollment was completed in May 2016. 519 patients were screened. The intention-to-treat (ITT) population of 416 patients was randomized at a 2:1 ratio to receive either: 5mg of fruquintinib orally once per day, on a three-weeks-on / one-week-off cycle, plus BSC (278 patients); or placebo plus BSC (138 patients). Randomization was stratified for prior anti-VEGF therapy and K-Ras gene status. The trial was concluded on January 17, 2017. The primary endpoint of median overall survival (OS) was 9.30 months [95% CI 8.18–10.45] in the fruquintinib group vs. 6.57 months [95% CI 5.88–8.11] in the placebo group, with a hazard ratio of 0.65 [95% CI: 0.51–0.83; two-sided p<0.001]. The secondary endpoint of median progression-free survival (PFS) was 3.71 months [95% CI 3.65–4.63] in the fruquintinib group vs. 1.84 months [95% CI 1.81–1.84] in the placebo group, with a hazard ratio of 0.26 [95% CI: 0.21–0.34; two-sided p<0.001]. Significant benefits were also seen in other secondary endpoints. The fruquintinib group disease control rate (DCR) was 62.2% vs. 12.3% for placebo (p<0.001), while the overall response rate (ORR) was 4.7% vs. 0% for placebo (p=0.012).

Safety and Tolerability - Results showed that fruquintinib had a manageable safety profile with lower off-target toxicities compared to other targeted therapies, and did not demonstrate the sometimes severe and fatal hepatotoxicity (liver toxicity) observed with other therapies in this disease setting. The most frequently reported fruquintinib-related grade greater then 3 adverse events included hypertension (21.2%), hand-foot skin reaction (10.8%), proteinuria (3.2%) and diarrhea (2.9%), all associated with VEGFR inhibition. Only 15.1% of patients discontinued treatment vs. 5.8% for placebo.

Comment: Chi-Med expects to complete the New Drug Application (NDA) submission for fruquintinib to the China Food and Drug Administration imminently. The Company also expects to initiate U.S. clinical studies in 2017.